Denigma

WRN

Symbol: WRN
Name: Werner syndrome, RecQ helicase-like
Alias: DKFZp686C2056; RECQ3; RECQL2; RECQL3
Entrez gene ID: 7486
Ensembl gene ID: ENSG00000165392
Species: Human (Taxid: 9606)

Functional description:
Encodes a DNA helicase with an exonuclease domain as well [8602509] and 3' to 5' exonuclease activity [9771700]; subcellular localisation of WRN is primarily nucleolar [Marciniak et al. 1008] ; stably associates with foci elements generating binding sites for RP-A (By similarity). [UniProt]

Observation:

Mutation in WRN causes Werner Syndrome which characteristics includes prematurely aged facies, scleroderma-like skin changes, cataracts, arteriosclerosis, subcutaneous calcification, and diabetes mellitus [McKusick et al. 1963; 5327241]. Inheritance is autosomal recessive and malignancy is frequent. THe frequency is 3 per million individuals in Japan [7460386].

Cells from a Werner heterozygote exit the cell cycle at a faster rate than do normal cells [8265666]. Loss of WRN promoter aberrant mitotic recombination [11316787].

The single nucleotide polymorphism rs1800392 in WRN has been associated with exceptional longevity in a plethora of genetic signatures [22279548]. WRN was found to be associated with longevity [10069711; 20855428; 20855428; 20855428 ;17903295; 22406557; 16405962; 16405962; 16405962; 20855428; 20855428; 20855428; 22279548]. WRN was found to be associated with longevity [24244950].



Interventions:
  • WRN mutation

    • Assays: Organismal Lifespan

    Longevity Associated Variants:
  • rs13251813 0.0002 [22406557]
  • rs1800392 0.000178635 [22279548]
  • rs3024239 0.000323577 [22279548]
  • rs13251813 0.0002 [22406557]
  • rs3087425 None [20855428]
  • rs1801195 None [20855428]
  • rs1346044 None [20855428]
  • rs1346044 None [10069711]
  • i1-C/T polymorphism None [16405962]
  • rs2725362 None [16405962]
  • rs1346044 None [16405962]
  • rs1800392 0.000708 [24244950]

    • Classification:
  • Aging Associated
  • Aging-Suppressor
  • Negative Aging-Suppressor
  • Longevity-Associated


    • Type:
  • Gene
  • Protein coding

    References:
  • 22279548: Genetic signatures of exceptional longevity in humans.
  • 5327241: Werner's syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process.
  • 16405962: Impact of genetic variations in the WRN gene on age related pathologies and mortality.
  • 10069711: Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians.
  • 20855428: Aging is accompanied by a progressive decrease of expression of the WRN gene in human blood mononuclear cells.
  • 17903295: Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study.
  • 22406557: Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: cross sectional and longitudinal studies.
  • 7460386: Family analysis of Werner's syndrome: a survey of 42 Japanese families with a review of the literature.
  • 8265666: The gene responsible for Werner syndrome may be a cell division "counting" gene.
  • 11316787: Loss of Werner syndrome protein function promotes aberrant mitotic recombination.


    • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

    • Homologs
  • WRN (9606)
  • WRN (9598)
  • WRN (9615)
  • Wrn (10090)
  • WRN (9031)
  • LOC569495 (7955)
  • wrn-1 (6239)
  • Os07g0681600 (4530)

    • Inparanoids
  • ENSP00000298139 (9606)
  • ENSMUSP00000033990 (10090)
  • ENSRNOP00000020835 (10116)
  • ENSMMUP00000029828 (9544)



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